.beta.-adrenoreceptor blocking agents have been widely used for curing or treatment of circulatory system diseases such as hypertension, angina pectoris and arrhythmia, and many of them are aryloxypropanolamines having a structure represented by the following formula ##STR2## wherein Ar represents a mother nucleus such as an aryl group and R represents a lower alkyl group or the like.
Various processes for preparation of a compound represented by the above formula (1) have been reported, and a typical one among them is a process shown by the following reaction formula ##STR3##
That is, the typical process is a process which comprises making an epoxy compound (3) act on an aryl alcohol (2) to prepare a glycidyl ether (4), and then making an amine (5) act thereon to prepare a desired aryloxypropanolamine (1).
In the above reactions, the reaction of the glycidyl ether (4) with the amine (5) as the second reaction generally proceeds with a good yield without occurrence of side reactions and thus there is no particular problem about the reaction, whereas the reaction of the aryl alcohol (2) with the epoxy compound (3) as the first reaction has, particularly in preparation of an optically active product, problems of lowering of optical purity and the like. ##STR4## [Please refer to Japanese Patent Publication No. 54317/1986; Japanese Laid-Open Patent Publication No. 167981/1982; J. Med. Chem., 15(3), 260-266(1972); etc.] ##STR5## Please refer to J. Am. Chem. Soc., 101, 3666(1979); Chem. Pharm. Bull., 35(9), 3691-3698(1987); etc.] ##STR6## Please refer to Japanese Laid-Open Patent Publication No. 208973/1985; Chem. Pharm. Bull., 35(9), 3691-3698(1987)] EQU Y=CF.sub.3 SO.sub.2 --
Please refer to J. Am. Chem. Soc., 101, 3666(1979)] ##STR7## [Please refer to WO190/1988] ##STR8## [Please refer to J. Med. Chem., 15(3), 260-266(1972); and J. Med. Chem., 23(10), 1122-1126(1980)]
Among these processes, the processes of the above (1) and (2) are processes wherein heating is carried out in the presence of a base such as sodium hydroxide or potassium carbonate, and thus are not suitable in case an aryl alcohol as a raw material is unstable against the base. For example, in case the raw material is an aryl alcohol having on the mother nucleus (Ar) a nitroxy group, an acylamino group, an alkylaminocarbonylalkoxy group, an alkoxycarbonyl group or the like, there is a drawback that these groups are liable to be eliminated or hydrolyzed by the base. Further, there is another drawback that when these processes are applied to preparation of an optically active product, optical purity of the resulting glycidyl ether is lowered.
On the other hand, in the process of the above (3), lowering of optical purity occurs only to a small extent, but it is necessary to prepare as a raw material an optically active glycidyl sulfonate and thus the process is industrially disadvantageous.
Further, the process of the above (4) has a drawback of low yield and formation of several by-products which are hard to remove.